Alexander Kapustin

Publications (2)19.4 Total impact

• Article: Proteasomal dysfunction in sporadic Parkinson's disease.

  Kevin St P McNaught, Tehone Jackson, Ruth JnoBaptiste, Alexander Kapustin, C Warren Olanow
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  ABSTRACT: The cause and mechanism of neuronal death in sporadic Parkinson's disease (PD) continue to elude investigators. Recently, alterations in proteasomal function have been detected in the brain of patients with the illness. The biochemical basis of the defect and its relevance to the disease process are now being studied. The available results suggest that proteasomal dysfunction could underlie protein accumulation, Lewy body formation, and neuron death in PD. The cause of proteasomal dysfunction is unknown at present, but this could relate to gene mutations, oxidative damage, ATP depletion, or the actions of environmental toxins. It remains to be established if proteasomal dysfunction plays a primary or a secondary role in the initiation or progression of the neurodegenerative process in PD.
  Neurology 06/2006; 66(10 Suppl 4):S37-49. · 8.31 Impact Factor
• Article: Brainstem pathology in DYT1 primary torsion dystonia.

  Kevin St P McNaught, Alexander Kapustin, Tehone Jackson, Toni-Ann Jengelley, Ruth Jnobaptiste, Pullanipally Shashidharan, Daniel P Perl, Pedro Pasik, C Warren Olanow
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  ABSTRACT: DYT1 dystonia is a severe form of young-onset dystonia caused by a mutation in the gene that encodes for the protein torsinA, which is thought to play a role in protein transport and degradation. We describe, for the first time to our knowledge, perinuclear inclusion bodies in the midbrain reticular formation and periaqueductal gray in four clinically documented and genetically confirmed DYT1 patients but not in controls. The inclusions were located within cholinergic and other neurons in the pedunculopontine nucleus, cuneiform nucleus, and griseum centrale mesencephali and stained positively for ubiquitin, torsinA, and the nuclear envelope protein lamin A/C. No evidence of inclusion body formation was detected in the substantia nigra pars compacta, striatum, hippocampus, or selected regions of the cerebral cortex. We also noted tau/ubiquitin-immunoreactive aggregates in pigmented neurons of the substantia nigra pars compacta and locus coeruleus in all four DYT1 dystonia cases, but not in controls. This study supports the notion that DYT1 dystonia is associated with impaired protein handling and the nuclear envelope. The role of the pedunculopontine and cuneiform nuclei, and related brainstem brainstem structures, in mediating motor activity and controlling muscle tone suggests that alterations in these structures could underlie the pathophysiology of DYT1 dystonia [corrected]
  Annals of Neurology 11/2004; 56(4):540-7. · 11.09 Impact Factor